The enzyme, dopamine-beta-hydroxylase (DBH), is unique among the enzymes involved in catecholamine biosynthesis in that release from neurons is a prominent aspect of its physiology. DBH is readily and repeatedly measureable in many mammals, including man, and could provide important insights into the metabolism of sympathoadrenal cells provided that the processes regulating the levels of enzyme in the circulatory component are understood. This project evaluates the processes regulating DBH in the circulatory compartment of the rat. We will assess the metabolic clearance rate (MCR) of rat DBH protein under defined circumstances; these include: (1) in rats with markedly different circulating DBH levels (genetically determined differences), (2) in rats with defined metabolic lesions, such as altered thyroid function and experimental diabetes, conditions known to be associated with reproducible changes in circulating DBH. These studies will provide insights into the rate of DBH production by sympathoadrenal cells. The potential for employing similar procedures in man to study the pathophysiology of diseases such as hypertension or neuropsychiatric disorders is present and will be evaluated. The processes involved in DBH metabolism by the liver also will be evaluated. Preliminary evidence suggests that circulating DBH is metabolized by a process involving desialylation and sequestration by hepatocytes, in common with several other circulating glycoproteins. Since extraneuronal disposal pathways are essential to correct interpretation of circulating DBH levels, elucidation of the specific mechanisms of DBH dedradation will be crucial to understanding the regulation of the circulating enzyme.